added robustness analysis

src/polygraph/models.py

@@ -279,24 +279,92 @@ def ism_score(model, seqs, batch_size, device="cpu", task=None):
 
     assert check_equal_lens(seqs)
 
+    # Predictions on original sequences
+    preds = predict(seqs=seqs, model=model, batch_size=batch_size, device=device)
+    assert preds.ndim < 3
+
+    # Select relevant task/cell type, or average predictions
+    if task is None:
+        if preds.ndim == 2:
+            preds = preds.mean(1, keepdims=True)
+    else:
+        preds = preds[:, [task]]
+
     # Mutate sequences
     ism = ISM(seqs)  # N x L x 4
 
     # Make predictions on mutated sequences
-    preds = predict(seqs=ism, model=model, batch_size=batch_size, device=device)
-    assert preds.ndim < 3
+    ism_preds = predict(seqs=ism, model=model, batch_size=batch_size, device=device)
 
     # Select relevant task/cell type, or average predictions
     if task is None:
-        if preds.ndim == 2:
-            preds = preds.mean(1)
+        if ism_preds.ndim == 2:
+            ism_preds = ism_preds.mean(1)
     else:
-        preds = preds[:, task]
+        ism_preds = ism_preds[:, task]
 
     # Reshape predictions : N, L, 4
-    preds = preds.reshape(len(seqs), len(ism) // (len(seqs) * 4), 4)
+    ism_preds = ism_preds.reshape(len(seqs), len(ism) // (len(seqs) * 4), 4)
 
     # Compute base-level importance score
-    preds = np.log2(preds / preds.mean(-1, keepdims=True))
+    preds = np.log2(ism_preds / preds)
     preds = np.abs(preds).max(-1)
     return preds
+
+
+def robustness(model, seqs, batch_size, device="cpu", task=None, aggfunc="mean"):
+    """
+    Get robustness scores for given sequence(s) using ISM
+
+    Args:
+        seqs (list, pd.DataFrame): List of sequences or dataframe
+            containing sequences in the column "Sequence".
+        model (nn.Sequential): trained model
+        batch_size (int): Batch size for inference
+        device (str, int): ID of GPU to perform inference.
+        aggfunc (str): Either 'mean' or 'max'. Determines how to aggregate the
+            effect of all possible single-base mutations.
+
+    Returns:
+        (pd.DataFrame): DataFrame of shape (n_seqs x n_outputs)
+    """
+    from polygraph.sequence import ISM
+    from polygraph.utils import check_equal_lens
+
+    assert check_equal_lens(seqs)
+
+    # Predictions on original sequences
+    preds = predict(seqs=seqs, model=model, batch_size=batch_size, device=device)
+    assert preds.ndim < 3
+
+    # Select relevant task/cell type, or average predictions
+    if task is None:
+        if preds.ndim == 2:
+            preds = preds.mean(1, keepdims=True)
+    else:
+        preds = preds[:, [task]]
+
+    # Mutate sequences
+    ism = ISM(seqs, drop_ref=True)  # N x L x 3
+
+    # Make predictions on mutated sequences
+    ism_preds = predict(seqs=ism, model=model, batch_size=batch_size, device=device)
+
+    # Select relevant task/cell type, or average predictions
+    if task is None:
+        if ism_preds.ndim == 2:
+            ism_preds = ism_preds.mean(1)
+    else:
+        ism_preds = ism_preds[:, task]
+
+    # Reshape predictions : N, Lx3
+    ism_preds = ism_preds.reshape(len(seqs), len(ism) // len(seqs))
+
+    # Compare mutated sequences to originals
+    deltas = np.abs((ism_preds / preds) - 1)
+
+    # Aggregate over all possible mutations
+    if aggfunc == "mean":
+        return np.mean(deltas, 1)
+    elif aggfunc == "max":
+        return np.max(deltas, 1)

src/polygraph/sequence.py

@@ -261,36 +261,50 @@ def fastsk(seqs, k=5, m=2):
     return np.array(kernel.get_train_kernel())
 
 
-def ISM(seqs):
+def ISM(seqs, drop_ref=False):
     """
     Perform in-silico mutagenesis on given DNA sequence(s)
 
     Args:
         seqs (str, list, pd.DataFrame): A DNA sequence, list of sequences
             or dataframe containing sequences in the column "Sequence".
+        drop_ref (bool): If True, do not return the original sequence.
 
     Returns:
         (list): A list of all possible single-base mutated sequences
             derived from the original sequences.
     """
     # ISM for a single sequence
     if isinstance(seqs, str):
-        return list(
-            np.concatenate(
-                [
-                    [seqs[:pos] + base + seqs[pos + 1 :] for base in STANDARD_BASES]
-                    for pos in range(len(seqs))
-                ]
+        if drop_ref:
+            return list(
+                np.concatenate(
+                    [
+                        [
+                            seqs[:pos] + base + seqs[pos + 1 :]
+                            for base in [x for x in STANDARD_BASES if x != b]
+                        ]
+                        for pos, b in enumerate(seqs)
+                    ]
+                )
+            )
+        else:
+            return list(
+                np.concatenate(
+                    [
+                        [seqs[:pos] + base + seqs[pos + 1 :] for base in STANDARD_BASES]
+                        for pos in range(len(seqs))
+                    ]
+                )
             )
-        )
 
     # Multiple sequences
     elif isinstance(seqs, list):
-        return list(np.concatenate([ISM(seq) for seq in seqs]))
+        return list(np.concatenate([ISM(seq, drop_ref=drop_ref) for seq in seqs]))
 
     # For a dataframe, copy the index
     elif isinstance(seqs, pd.DataFrame):
-        return ISM(seqs.Sequence.tolist())
+        return ISM(seqs.Sequence.tolist(), drop_ref=drop_ref)
 
     else:
         raise TypeError("seqs must be a string, list or dataframe.")